Disease relevance of ME2303

• Against colon adenocarcinoma 26, ME2303 induced cure in 16 of 20 mice at doses of 35 to 71 mumol/kg, whereas no cure was observed with ADM [1].
• ME2303 was also more effective than ADM against human leukemia CCRF-CEM resistant to vinblastine, human ovarian carcinoma A2780 resistant to ADM, human epidermoid carcinoma KB cells resistant to colchicine, and mouse leukemia P388 resistant to ADM and vincristine [1].
• ME2303 given i.p. or i.v. on Day 1 or Days 1, 5, and 9 was also effective against i.p.-implanted P388 leukemia cells, and higher incidences of cure were obtained than with ADM [1].
• For example, human myelogenous leukemia K562 resistant to ADM (K562/ADM) was only 2.8-fold more resistant to ME2303, while the cells were 200-fold more resistant to ADM when the values for the concentration of drug required for 50% inhibition of cell growth were compared [1].
• ME2303 administered i.v. on Days 1, 8, 15, and 22 showed prominent antitumor activity against s.c.-implanted colon adenocarcinomas 26 and 38, Lewis lung carcinoma, B16 melanoma, and M5076 sarcoma [1].

High impact information on ME2303

• Differential intracellular processing of the anthracycline drug ME2303 in doxorubicin-sensitive (A2780) and -resistant (A2780AD) human ovarian cancer cells as studied with confocal laser scanning microscopy and image analysis [2].
• In both cell types, ME2303 was characterised by strong nuclear membrane and perinucleolar fluorescence and as a localised punctate pattern within the nucleus [2].
• A2780AD cells accumulated ME2303 in their nuclei at a much reduced rate compared to the doxorubicin-sensitive cells, and ME2303 efflux from resistant cell nuclei was approximately twice as fast as from A2780 cells [2].
• ME2303 may be active against hepatic metastases if it is administered by multiple injections [3].
• Likewise, ME2303 was more effective against Lu-24 human small cell carcinoma and MX-1 human medullary tubular adenocarcinoma than ADM [4].

Chemical compound and disease context of ME2303

• Comparison of antitumor activity of new anthracycline analogues, ME2303, KRN8602, and SM5887 using human lung cancer cell lines [5].

Biological context of ME2303

• The LD50 value of ME2303 was about 140 mg/kg i.v. in mice and this value was about 7-fold higher than that of ADM [6].
• The mean plasma concentrations of M2 were detected up to 8 and 4 h after i.v. administration of DA-125 and ME2303, respectively, to mice and were significantly higher for DA-125 than ME2303, resulting in a considerably greater AUC of M2 (148 against 27.1 micrograms min mL(-1)) after i.v. administration of DA-125 [7].

Anatomical context of ME2303

• Laser scanning confocal microscopy has been used to follow the uptake and efflux of the 2-fluoroglycoside of doxorubicin, ME2303, in live cultures of the human ovarian cancer cell line A2780 and its doxorubicin-resistant variant A2780AD [2].
• ME2303 was rapidly metabolized and disappeared rapidly from the plasma, liver and bone marrow [8].
• Effects of fluoro-doxorubicin (ME2303) on microtubules: influence of different classes of microtubule-associated proteins [9].

Associations of ME2303 with other chemical compounds

• The mean plasma concentrations of M4 were detected up to 8 h after i.v. administration of both DA-125 and ME2303 to mice, and were higher after i.v. administration of DA-125 than ME2303, resulting in a considerably greater AUC of M4 (197 against 61.9 micrograms min mL(-1)) after i.v. administration of DA-125 [7].

Gene context of ME2303

• These results suggest that OP, ME2303 and CPT-11 could be active in patients with, NSCLC clinically resistant to CDDP [10].

Analytical, diagnostic and therapeutic context of ME2303

• From ECG changes, it seems that ME2303 did not show any effect on the heart in acute toxicity [6].

References